Starglo: This phase III trial aims to evaluate the effectiveness of two targeted therapy-chemotherapy combinations in patients with Diffuse Large B-cell LymphomaA Phase III, Open-Label, Multicenter, Randomized Study Evaluating the Efficacy and Safety of Glofitamab in Combination With Gemcitabine Plus Oxaliplatin Versus Rituximab in Combination With Gemcitabine and Oxaliplatin in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Exclusion

• Patient has failed only one prior line of therapy and is a candidate for stem cell transplantation
• History of transformation of indolent disease to DLBCL
• High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, and high-grade B-cell lymphoma not otherwise specified, as defined by 2016 WHO guidelines
• Primary mediastinal B-cell lymphoma
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies (or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products
• Contraindication to obinutuzumab, rituximab, gemcitabine or oxaliplatin, or tocilizumab
• Prior treatment with glofitamab or other bispecific antibodies targeting both CD20 and CD3
• Peripheral neuropathy assessed to be Grade >1 according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 at enrollment
• Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational agent for the purposes of treating cancer within 2 weeks prior to first study treatment
• Treatment with monoclonal antibodies for the purposes of treating cancer within 4 weeks prior to first study treatment
• Primary or secondary central nervous system (CNS) lymphoma at the time of recruitment or history of CNS lymphoma
• Current or history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
• Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection (as evaluated by the investigator) within 4 weeks prior to the first study treatment
• Positive SARS-CoV-2 infection within 30 days prior to the first study treatment, including asymptomatic SARS-CoV-2 infection
• Documented SARS-CoV-2 infection within 6 months of first study treatment
• Suspected or latent tuberculosis
• Positive for hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV)
• Known or suspected chronic active Epstein-Barr viral infection
• Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
• Known history of progressive multifocal leukoencephalopathy
• Adverse events from prior anti-cancer therapy not resolved to Grade 1 or better (with the exception of alopecia and anorexia)
• Administration of a live, attenuated vaccine within 4 weeks before first study treatment administration or anticipation that such a live, attenuated vaccine will be required during the study
• Prior solid organ transplantation
• Prior allogeneic stem cell transplant
• Active autoimmune disease requiring treatment
• Prior treatment with systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents), within 4 weeks prior to first dose of study treatment
• Corticosteroid therapy within 2 weeks prior to first dose of study treatment (exceptions defined by study protocol)
• Recent major surgery (within 4 weeks before the first study treatment) other than for diagnosis
• Clinically significant history of cirrhotic liver disease